An ACE2-Based Decoy Inhibitor Effectively Neutralizes SARS-CoV-2 Omicron BA.5 Variant

Autor: Haoran Zhang, Bing Hu, Panjing Lv, Yahui Liu, Meng Guo, Zhi Wu, Kangping Zhou, Minglu Dai, Xiao Yu, Zhang Liu, Bo Yu, Liqiong Xu, Min Guo, Kun Cai, Yan Li
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Viruses, Vol 14, Iss 11, p 2387 (2022)
Druh dokumentu: article
ISSN: 1999-4915
46704027
DOI: 10.3390/v14112387
Popis: The recently circulating SARS-CoV-2 Omicron BA.5 is rampaging the world with elevated transmissibility compared to the original SARS-CoV-2 strain. Immune escape of BA.5 was observed after treatment with many monoclonal antibodies, calling for broad-spectrum, immune-escape-evading therapeutics. In retrospect, we previously reported Kansetin as an ACE2 mimetic and a protein antagonist against SARS-CoV-2, which proved potent neutralization bioactivity on the Reference, Alpha, Beta, Delta, and Omicron strains of SARS-CoV-2. Since BA.5 is expected to rely on the interaction of the Spike complex with human ACE2 for cell entry, we reasonably assumed the lasting efficacy of the ACE2-mimicking Kansetin for neutralizing the new SARS-CoV-2 variant. The investigation was accordingly performed on in vitro Kansetin-Spike binding affinity by SPR and cell infection inhibition ability with pseudovirus and live virus assays. As a result, Kansetin showed dissociation constant KD and half inhibition concentration IC50 at the nanomolar to picomolar level, featuring a competent inhibition effect against the BA.5 sublineage. Conclusively, Kansetin is expected to be a promising therapeutic option against BA.5 and future SARS-CoV-2 sublineages.
Databáze: Directory of Open Access Journals
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